My assignment in this chapter is to bring to your attention some features of the pathophysiology of functional headaches which may be useful in planning their management by behavioral techniques. Head pain may occur not only when the head is traumatized or inflamed or distorted by tumor but also when its complicated machinery strains to meet overwhelming mental and emotional distress. It is this “cranial angina” which behavioral therapy may be able to modify, even as help with changes in lifestyle and physical exertion may aid the Type A man with “angina of the heart.” The brain really is, amongst its many other functions, the health care system or behavioral therapist for the body. But, as you all know, even behavioral therapists can get tired or have difficult, maybe even painful days.

Behavior, at long last, may be taking its proper place in Western medicine. The study of behavior in medicine has even spawned a new discipline, sometimes called behavioral medicine. In the broadest sense, behavioral medicine refers to the application of behavioral science knowledge and techniques to the understanding of physical health and illness and to prevention, diagnosis, treatment, and rehabilitation. In this chapter, we discuss behavioral medicine only in terms of the application of behavioral therapy and applied analysis to these same areas. An astonishing number of studies have been published in this area, mostly in the past 10 years, and the numbers are increasing exponentially.

This paper considers the use of biofeedback methods for the treatment of migraine headache. The incidence of headache as a clinical problem is first examined. The pathophysiological basis of migraine and the preferred methods of treatment are presented. Next, basic principles of controlled treatment evaluation are discussed. Two biofeedback procedures for the treatment of migraine are then considered: hand warming and cephalic pulse amplitude reduction. The therapeutic rationale for each treatment is presented and data from all relevant controlled experiments are summarized. It is concluded that there is no evidence for specific effects of learned hand warming, but that a specific component might be present for learned cephalic vasoconstriction.

Biofeedback is one of the major treatment technologies in behavioral medicine. In fact, the initial use of the term behavioral medicine was in reference to the use of biofeedback in the treatment of medical disorders (Birk, 1973). Although many other techniques have been used in the behavioral treatment of numerous disorders, a large proportion of the behavioral medicine literature involves biofeedback. In fact, previous reviews of the literature of behavioral medicine have separated the treatment literature into biofeedback (Blanchard & Epstein, 1977) and non-biofeedback (Epstein, Katz, & Zlutnick, 1979) studies.

The themes of this chapter are that (1) hypnosuggestive procedures can be effective in reducing pain and (2) these procedures should be incorporated into the armamentarium of all professionals who treat pain. I will first summarize representative studies that illustrate how hypnosuggestive procedures can be used and how effective they can be in the alleviation of surgical and postsurgical pain, back pain, headaches and migraine, cancer pain, burn pain, dental pain, and childbirth pain. Throughout this review, I will try to be directly helpful to health professionals by presenting verbatim examples of hypnosuggestive procedures that can be useful in treating acute and chronic pain.

The word stress is a Latin derivative which has existed in the English language for centuries. Originally, it denoted hardship or adversity. Later, stress was used to denote a “force, pressure, strain or strong effort” applied to an object or person including his “organs or mental powers” (Hinkle, 1974b; Onions, 1933). In the biological sciences, the term stress has a connotative rather than a denotative function, suggesting, on the one hand, external stimulus characteristics which tend to upset the “milieu interieur” of the organism and, on the other, characteristics of the organism’s response to such stimulus characteristics. Stressful stimuli include mechanical and chemical trauma, toxins, bacterial and viral pathogens, loud noises, monotonous work, and threats to or changes in social relationships. The general adaptation syndrome exemplifies organismic responses which qualify as stress (Selye, 1946, 1976). This syndrome refers to a sequence of nonspecific bodily reactions which occur in response to generalized noxious stimuli. The development of the syndrome depends on the functional integrity of the pituitary and adrenal glands and is characterized by the secretion of adrenalin, noroadrenalin, and adrenocortical hormones.

Despite over 20 years of research, the clinical effectiveness of biofeedback has not been established. Nevertheless the use of biofeedback techniques has been promulgated as a beneficial form of treatment for a wide variety of disorders. Although some biofeedback applications seem to be highly effective, the research underlying many other types of application remains equivocal. This article addresses a number of the more important critical issues, both methodological and conceptual that are in need of resolution before biofeedback can be promoted as a clinically valid treatment procedure on as wide a basis as is presently the case.

Most products of food metabolism have adverse effects on health if their concentrations in blood and extra- and intracellular fluids exceed narrow physiologic limits. Homeostasis, the maintenance of normal concentrations, is achieved by a vast number of genetically determined enzymatic processes that regulate digestion, absorption, transport, intermediate metabolism, and excretion.

This report presents findings from a two-year follow-up of chronic tension headache sufferers treated either with stress-coping training (cognitive therapy, N = 11) or electromyographic biofeedback (N = 8). Clients who had received stress-coping training reported that two years following treatment they continued to use the coping strategies they had been taught, and daily headache recordings indicated they were still significantly improved ( p < .005). About one-half of the clients treated with biofeedback were substantially improved following treatment, with the remaining clients showing minor improvements or increases in headache symptoms. These mixed outcomes were still evident at two-year follow-up, with three of four clients maintaining improvements and the remaining clients showing, at best, minor reductions in headache symptoms. This longterm maintenance of treatment gains following stress-coping training suggests that cognitive therapy deserves the increased attention of investigators interested in the long-term maintenance of therapeutic gains.

Summary

Synopsis: Domperidone1 is a dopamine antagonist that does not readily enter the central nervous system. Given parenterally or orally it increases gastric emptying of liquids and increases lower oesophageal sphincter pressure in healthy subjects. The antiemetic and pharmacodynamic profile of domperidone is similar to that of metoclopramide, although domperidone has a lower propensity to cause extrapyramidal side effects. Domperidone effectively alleviates symptoms of chronic postprandial dyspepsia and nausea and vomiting due to a wide variety of underlying causes and in some studies has been superior to metoclopramide. Vomiting associated with the administration of moderately emetic cytotoxic drugs is controlled in the majority of patients. Alleviation of the dose-limiting peripheral side effects (nausea and vomiting) of the anti-Parkinsonian drugs bromocriptine and levodopa, enables a higher optimum dose, with consequent improvement in Parkinsonian symptoms. Domperidone does not aggravate the extrapyramidal side effects of neuroleptic drugs. Control of cytotoxic-induced, and postprandial nausea and vomiting in children has been achieved with domperidone without evidence of extrapyramidal side effects. Indeed, side effects have seldom occurred with therapeutic doses of domperidone.

Pharmacodynamic Studies: Domperidone is a dopamine antagonist with antiemetic properties similar to those of metoclopramide and certain neuroleptic drugs. Unlike these drugs, however, domperidone does not readily cross the blood-brain barrier and seldom causes extrapyramidal side effects.

The wide dissociation between the peripheral and central effects of domperidone has been clearly demonstrated in animal studies by the low brain concentrations after systemic administration, the lack of effect on plasma concentrations of the dopamine metabolite, homovanillic acid, the marked differences in the effect of intracerebrally and systemically administered domperidone in antagonising the behavioural effects of dopamine, and the wide difference in the intravenous dosage needed to antagonise the peripheral (emetic) and central effects of apomorphine.

Studies in humans have shown intravenous and oral domperidone to increase lower oesophageal sphincter pressure in healthy subjects, to increase the duration of antral and duodenal contractions, to increase the gastric emptying of liquids and semi-solids such as a barium meal, and to shorten the stationary phase for solids in healthy subjects and in patients in whom it was delayed. The effect in patients with histologically confirmed reflux oesophagitis has, however, been equivocal.

Administered orally or intravenously, domperidone is a potent stimulant of prolactin release in both males and females, although peak concentrations of prolactin are consistently higher in females than in males. The increase in plasma prolactin occurs in healthy subjects, in hyperprolactinaemia after childbirth, and in hypothyroid patients, but domperidone has little effect on plasma prolactin in patients with a prolactin-secreting tumour. Domperidone does not affect plasma growth hormone or aldosterone concentrations.

Pharmacokinetics: Peak plasma concentrations are attained at 10 to 30 minutes after intramuscular and oral administration, and at 1 to 2 hours after rectal administration of suppositories. Systemic bioavailability of intramuscular domperidone is about 90%, whereas that of oral domperidone is 13 to 17%. The low systemic bioavailability is probably due to ‘first-pass’ hepatic and gut wall metabolism. Oral bioavailability is increased when domperidone is administered 90 minutes after a meal, but is decreased by prior administration of cimetidine or sodium bicarbonate.

Distribution data in humans are lacking, but studies in rats with radiolabelled drug have shown wide distribution in body tissues except the central nervous system, where only low concentrations occur. Small amounts of radioactivity cross the placental barrier.

In humans, the apparent volume of distribution is 440L, or 5.7 L/kg, after intravenous administration. The human plasma protein binding of tritiated domperidone is about 92%.

Domperidone undergoes rapid and extensive biotransformation by hydroxylation and oxidative N-dealkylation. The proportion of the drug remaining unchanged is small, accounting for only 1.4% of the total urinary radioactivity and 10% of the faecal radioactivity. After oral administration of 40mg l4C-domperidone in healthy volunteers, 31% of the radioactivity is excreted in the urine and 60% in the faeces over a period of 4 days. Practically all of the urinary radioactivity is recovered within the first 24 hours, with only 1.4% (0.43% of the dose) present as unchanged drug. The greatest proportion of that part of the dose recovered in the urine is in the form of glucuronide conjugates of the metabolite formed by oxidative N-dealkylation. The elimination half-life of domperidone is 7.5 hours in healthy subjects and is prolonged to up to 20.8 hours in patients with severe renal dysfunction. However, since renal clearance is small compared with total plasma clearance (700 ml/minute), accumulation should not occur in renal dysfunction.

Therapeutic Trials: Domperidone has been extensively studied in the treatment of a cluster of symptoms commonly referred to as chronic dyspepsia and in the treatment and prevention of nausea and vomiting resulting from a variety of causes.

In studies comparing oral domperidone 30 to 80mg with placebo or with an equal dose of metoclopramide in patients with functional postprandial dyspepsia, domperidone has been superior to placebo where adequate numbers of patients have been studied and at least as effective as metoclopramide. Assessment has usually been by changes in symptom scores and global assessment.

Studies in patients with reflux oesophagitis confirmed by endoscopy and/or biopsy, have usually shown no difference between the effect of domperidone 30 to 80mg daily and placebo as assessed by repeat endoscopy, biopsy or acid infusion tests. However, domperidone has relieved some symptoms to a greater extent than placebo.

Preliminary studies in endoscopically confirmed gastric ulcer have reported domperidone 60mg to be more effective than placebo in promoting healing. In a single study, lasting only 3.5 weeks, no significant difference between the rates of healing with cimetidine 1g daily and domperidone 50mg daily could be detected. Further well designed studies of longer duration are needed to determine the role of domperidone in promoting healing of gastric ulcers.

Domperidone has been shown to be an effective antiemetic in patients with postoperative vomiting, when administered after the first vomiting episode. However, when administered before induction or near the end of anaesthesia, postoperative emetic sequelae have not consistently been prevented. The reasons for the indifferent efficacy of domperidone in these studies is unclear, but may be associated with the route of administration, narcotic premedication and the time between administration and the postoperative recovery period.

Nausea and vomiting associated with cytotoxic drug therapy has generally been effectively controlled by parenteral domperidone administered immediately before the cytotoxic regimen. Domperidone has usually been found to be superior to placebo and comparable with metoclopramide. As might be expected, symptoms accompanying the use of strongly emetic drugs like mustine (mechlorethamine; nitrogen mustard) and dacarbazine have been controlled less often than those associated with moderately emetic cytotoxic drugs.

In children, domperidone has been successfully used to treat cytotoxic-induced vomiting, that associated with various underlying conditions such as gastroenteritis, gastritis and acetonaemia, and acute and persistent symptoms arising after food. There have been no reported instances of extrapyramidal side effects.

When administered concomitantly with the anti-Parkinsonian drug, bromocriptine, domperidone has suppressed peripheral dose-limiting side effects (nausea and vomiting), thus enabling patients to tolerate higher doses of bromocriptine. Gastrointestinal symptoms induced by levodopa have also been alleviated by oral domperidone. The beneficial central effects of the anti-Parkinsonian drugs were not aggravated by domperidone, and extrapyramidal side effects attributable to domperidone were not reported.

Side Effects: Domperidone has been particularly well tolerated and has seldom caused any important side effects. There have been no extrapyramidal side effects reported during controlled therapeutic trials with domperidone, although a few anecdotal reports of such effects have been published.

Dosage: In adults with chronic postprandial dyspepsia the usual adult dose is 10mg 3 or 4 times daily before meals and at night. In children 0.3 mg/kg bodyweight is recommended. In acute vomiting requiring parenteral administration the daily dose should not exceed 1 mg/kg bodyweight. When administered rectally, the adult dosage is 60mg 2 to 4 times daily. In children younger than 2 years, a 10mg suppository should be inserted 2 to 4 times daily. In older children the usual daily rectal dose is 60mg in those aged 2 to 4 years, 90mg in those 4 to 6 years and 120mg in those over 6 years.

Adult patients with acute symptoms who are able to take the drug orally should be given 20 to 40mg 3 or 4 times daily. Children should receive 0.6 mg/kg 3 to 4 times daily.